Research in this laboratory is directed to the understanding of mechanisms of antibody diversity at the molecular, genetic and cellular levels. Antigenic determinants on different regions of immnoglobulin molecules have been identified for six of the eight immunoglobulin classes present in the mouse. Some myeloma proteins bind specific haptens. Mice immunized with the same haptens frequently produce antibodies which have idiotypes similar to those of the myeloma proteins. Genetic studies of positive and negative idiotype strains show that those idiotypes are controlled by V-region structural genes many of which are linked to allotype. The number of genes required for the diversity of antibody is determined by mapping the linked VH-CH genes and determining their recombination frequency. However the validity of these studies is questioned by the finding that Vl genes (not linked to VH) play an important role in determining the idiotype. Idiotypic markers are particularly valuable for genetic studies of immunoglobulins at the cellular level. Different cells have been examined for receptor molecules carrying idiotypes similar to those present in normal antibodies and myeloma proteins. At present in vitro and in vivo studies for specific idiotypes are being done. BIBLIOGRAPHIC REFERENCES: Morse, H.C. III, Neiders, M.E., Lieberman, R., Lawton, A.R. III and Asofsky, R.: Murine plasma-cells secreting more than one class immunoblogulin heavy chain. II. SAMM 368-A plasmacytoma secreting IGG2b-K and IgA-K immunoglobulins which do not share idiotypic determinants. J. Immunol. 118: 1682, 1977. Lieberman, R., Humphrey, W., Jr., and Chien, C.C.: Identification and genetics of gamma l light chain allotype in the mouse. Immunogenetics. In press, 1977.